The proposed project is a neurophysiological and anatomical investigation of the mechanism by which unilateral denervation of a frog sartorius muscle causes increased synaptic effectiveness at neuromuscular junctions in the contralateral sartorius. This enhanced effectiveness is not due to increased synaptic size, which remains unchanged. Instead, transmitter release per unit nerve terminal length increases up to 8 times in contralateral muscles. Synaptic effectiveness will be assessed by estimating the safety margin for neuromuscular transmission and by using intracellular recording to measure quantal content and other release parameters. Light and thin section electron microscopy will be used to search for morphological correlates of synaptic effectiveness at single identified endplates whose transmitter release properties have been analyzed. Freeze fracture electron microscopy will also be used to correlate average synaptic effectiveness with intramembranous ultrastructure. The following hypotheses for the mechanism of enhanced release will be tested: 1) alteration in ultrastructure, especially in the number of arrangement of presynaptic active zones; 2) altered intraterminal Ca2+ buffering; 3) prolongation of the presynaptic action potential; 4) altered nerve terminal membrane surface charge; 5) altered Ca2+ channel properties. Contralateral denervation also causes an increase in polyneuronal innervation, i.e., the convergence of multiple presynaptic inputs onto the same postsynaptic site. The possibility will be tested that this increase is only an apparent one, resulting from the enhanced detectibility of previously present, but undetectably weak polyneuronal inputs. There is no evidence that contralateral denervation causes motor nerve sprouting as previously suggested in related experiments. This project should advance our understanding of how peripheral synapses are regulated and what role these regulatory processes play in normal neuromuscular function and disease-related changes. The major significance of this study, however, may lie in its contribution to understanding comparable synaptic plasticity in the central nervous system. Such plasticity seems to play an important role in the development and maintenance of the brain and its repair following injury.